Abstract
BACKGROUND:CREB binding protein (CBP) and its close paralogue p300 are transcriptional coactivators with intrinsic acetyltransferase activity.Both CBP/p300 play critical roles in development and diseases.The enzymatic and biological functions of CBP/p300 are tightly regulated by themselves and by external factors.However,a comprehensive up-to-date review of the intramolecular and intermolecular regulations is lacking.OBJECTIVE:To summarize the molecular mechanisms regulating CBP/p300s functions.METHODS:A systematic literature search was conducted using the PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) for literatures published during 1985-2018.Keywords “CBP regulation” or “p300 regulation” were used for the search.RESULTS:The functions of CBP/p300,especially their acetyltransferase activity and chromatin association,are regulated both intramolecularly by their autoinhibitory loop (AIL),bromodomain,and PHD-RING region and intermolecularly by their interacting partners.The intramolecular mechanisms equip CBP/p300 with the capability of self-regulation while the intermolecular mechanisms allow them to respond to various cell signaling pathways.CONCLUSION:Investigations into those regulation mechanisms are crucial to our understanding of CBP/p300s role in development and pathogenesis.Pharmacological interventions targeting these regulatory mechanisms have therapeutic potentials.
基金项目
This work was supported in part by grants from NIH/NCI(CA204020)
Leukemia &Lymphoma Society(1339-17)
NETL
NSTL
维普
万方数据